Very frequent loss of heterozygosity (LOH) on chromosome 3p has been found in human renal cell carcinoma (RCC). In the present study, we examined LOH at the retinoblastoma (RB), mutated in colorectal cancer (MCC) and adenomatous polyposis coli (APC) tumour suppressor genes loci, and mutations of the H-, K-, and N-ras oncogenes. We performed these studies using the polymerase chain reaction (PCR) method followed by restriction fragment length polymorphism (RFLP) and single-strand conformation polymorphism (SSCP) analyses. LOH was detected in 2 of 11 (18.2%), and 2 of 14 (14.3%) informative cases at the MCC and APC loci, respectively, and in none of 15 informative cases at the RB locus in 25 RCCs. LOH at the MCC was accompanied by LOH at the APC locus in two RCCs. No mutation was detected in H-, K-, and N-ras genes in 39 RCCs. Thus, alterations of the known tumour suppressor genes and the ras oncogenes were infrequent events in RCC. The results suggest that the genetic pathway in the genesis of RCC differs considerably from that of other common human carcinomas.